Search Results
You are looking at 1 - 9 of 9 items for
- Author: Nicola Fazio x
- Refine by Access: All content x
Search for other papers by Vito Amoroso in
Google Scholar
PubMed
Search for other papers by Giorgio Maria Agazzi in
Google Scholar
PubMed
Search for other papers by Elisa Roca in
Google Scholar
PubMed
Search for other papers by Nicola Fazio in
Google Scholar
PubMed
Search for other papers by Alessandra Mosca in
Google Scholar
PubMed
Search for other papers by Marco Ravanelli in
Google Scholar
PubMed
Search for other papers by Francesca Spada in
Google Scholar
PubMed
Search for other papers by Roberto Maroldi in
Google Scholar
PubMed
Search for other papers by Alfredo Berruti in
Google Scholar
PubMed
Department of Molecular and Translational Medicine, Division of Biology and Genetics, University of Brescia, Brescia, Italy
Search for other papers by Chiara Alessandra Cella in
Google Scholar
PubMed
Metal Targeted Therapy & Immunology lab, Childrens’ cancer institute, Sydney, NSW, Australia
Search for other papers by Riccardo Cazzoli in
Google Scholar
PubMed
Search for other papers by Nicola Fazio in
Google Scholar
PubMed
Search for other papers by Giuseppina De Petro in
Google Scholar
PubMed
Search for other papers by Germano Gaudenzi in
Google Scholar
PubMed
Search for other papers by Silvia Carra in
Google Scholar
PubMed
Search for other papers by Mauro Romanenghi in
Google Scholar
PubMed
Search for other papers by Francesca Spada in
Google Scholar
PubMed
Search for other papers by Ilaria Grossi in
Google Scholar
PubMed
Search for other papers by Isabella Pallavicini in
Google Scholar
PubMed
Department of Oncology and Hemato-Oncology, University of Milan, Milan, Italy
Search for other papers by Saverio Minucci in
Google Scholar
PubMed
Department of Medical Biotechnology and Translational Medicine, University of Milan, Milan, Italy
Search for other papers by Giovanni Vitale in
Google Scholar
PubMed
Neuroendocrine tumors (NETs) are highly vascularized malignancies in which angiogenesis may entail cell proliferation and survival. Among the emerging compounds with antivascular properties, cabozantinib (CAB) appeared promising. We analyzed the antitumor activity of CAB against NETs utilizing in vitro and in vivo models. For cell cultures, we used BON-1, NCI-H727 and NCI-H720 cell lines. Cell viability was assessed by manual count coupled with quantification of cell death, performed through fluorescence-activated cell sorting analysis as propidium iodide exclusion assay. In addition, we investigated the modulation of the antiapoptotic myeloid cell leukemia 1 protein under CAB exposure, as a putative adaptive pro-survival mechanism, and compared the responses with sunitinib. The activity of CAB was also tested in mouse and zebrafish xenograft tumor models. Cabozantinib showed a dose-dependent and time-dependent effect on cell viability and proliferation in human NET cultures, besides a halting of cell cycle progression for endoduplication, never reported for other tyrosine kinase inhibitors. In a transplantable zebrafish model, CAB drastically inhibited NET-induced angiogenesis and migration of implanted cells through the embryo body. CAB showed encouraging activity in NETs, both in vitro and in vivo models. On this basis, we envisage future research to further investigate along these promising lines.
Search for other papers by James Yao in
Google Scholar
PubMed
Search for other papers by Abhishek Garg in
Google Scholar
PubMed
Search for other papers by David Chen in
Google Scholar
PubMed
Search for other papers by Jaume Capdevila in
Google Scholar
PubMed
Search for other papers by Paul Engstrom in
Google Scholar
PubMed
Search for other papers by Rodney Pommier in
Google Scholar
PubMed
Search for other papers by Eric Van Cutsem in
Google Scholar
PubMed
Search for other papers by Simron Singh in
Google Scholar
PubMed
Search for other papers by Nicola Fazio in
Google Scholar
PubMed
Search for other papers by Wei He in
Google Scholar
PubMed
Search for other papers by Markus Riester in
Google Scholar
PubMed
Search for other papers by Parul Patel in
Google Scholar
PubMed
Search for other papers by Maurizio Voi in
Google Scholar
PubMed
Search for other papers by Michael Morrissey in
Google Scholar
PubMed
Search for other papers by Marianne Pavel in
Google Scholar
PubMed
Search for other papers by Matthew Helmut Kulke in
Google Scholar
PubMed
Neuroendocrine tumors (NETs) have historically been subcategorized according to histologic features and the site of anatomic origin. Here, we characterize the genomic alterations in patients enrolled in three phase 3 clinical trials of NET of different anatomic origins and assess the potential correlation with clinical outcomes. Whole-exome and targeted panel sequencing was used to characterize 225 NET samples collected in the RADIANT series of clinical trials. Genomic profiling of NET was analyzed along with nongenomic biomarker data on the tumor grade and circulating chromogranin A (CgA) and neuron-specific enolase (NSE) levels from these patients enrolled in clinical trials. Our results highlight recurrent large-scale chromosomal alterations as a common theme among NET. Although the specific pattern of chromosomal alterations differed between tumor subtypes, the evidence for generalized chromosomal instability (CIN) was observed across all primary sites of NET. In pancreatic NET, although the P value was not significant, higher CIN suggests a trend toward longer survival (HR, 0.55, P = 0.077), whereas in the gastrointestinal NET, lower CIN was associated with longer survival (HR, 0.44, P = 0.0006). Our multivariate analyses demonstrated that when combined with other clinical data among patients with progressive advanced NETs, chromosomal level alteration adds important prognostic information. Large-scale CIN is a common feature of NET, and specific patterns of chromosomal gain and loss appeared to have independent prognostic value in NET subtypes. However, whether CIN in general has clinical significance in NET requires validation in larger patient cohort and warrants further mechanistic studies.
Department of Biomedical Sciences, Cluster for Molecular Imaging, University of Copenhagen, Copenhagen, Denmark
Search for other papers by Esben Andreas Carlsen in
Google Scholar
PubMed
Search for other papers by Nicola Fazio in
Google Scholar
PubMed
Search for other papers by Dan Granberg in
Google Scholar
PubMed
Search for other papers by Simona Grozinsky-Glasberg in
Google Scholar
PubMed
Search for other papers by Hojjat Ahmadzadehfar in
Google Scholar
PubMed
Search for other papers by Chiara Maria Grana in
Google Scholar
PubMed
Search for other papers by Wouter T Zandee in
Google Scholar
PubMed
Search for other papers by Jaroslaw Cwikla in
Google Scholar
PubMed
Search for other papers by Martin A Walter in
Google Scholar
PubMed
Search for other papers by Peter Sandor Oturai in
Google Scholar
PubMed
Search for other papers by Anja Rinke in
Google Scholar
PubMed
Search for other papers by Andrew Weaver in
Google Scholar
PubMed
Search for other papers by Andrea Frilling in
Google Scholar
PubMed
Search for other papers by Sara Gritti in
Google Scholar
PubMed
Search for other papers by Anne Kirstine Arveschoug in
Google Scholar
PubMed
Search for other papers by Amichay Meirovitz in
Google Scholar
PubMed
Departments of Surgical Gastroenterology and Clinical Endocrinology, Rigshospitalet, Copenhagen, Denmark
Search for other papers by Ulrich Knigge in
Google Scholar
PubMed
Department of Clinical Science, University of Bergen, Bergen, Norway
Search for other papers by Halfdan Sorbye in
Google Scholar
PubMed
Peptide receptor radionuclide therapy (PRRT) is an established treatment of metastatic neuroendocrine tumors grade 1–2 (G1–G2). However, its possible benefit in high-grade gastroenteropancreatic (GEP) neuroendocrine neoplasms (NEN G3) is largely unknown. We therefore aimed to assess the benefits and side effects of PRRT in patients with GEP NEN G3. We performed a retrospective cohort study at 12 centers to assess the efficacy and toxicity of PRRT in patients with GEP NEN G3. Outcomes were response rate, disease control rate, progression-free survival (PFS), overall survival (OS) and toxicity. We included 149 patients (primary tumor: pancreatic n = 89, gastrointestinal n = 34, unknown n = 26). PRRT was first-line (n = 30), second-line (n = 62) or later-line treatment (n = 57). Of 114 patients evaluated, 1% had complete response, 41% partial response, 38% stable disease and 20% progressive disease. Of 104 patients with documented progressive disease before PRRT, disease control rate was 69%. The total cohort had median PFS of 14 months and OS of 29 months. Ki-67 21–54% (n = 125) vs Ki-67 ≥55% (n = 23): PFS 16 vs 6 months (P < 0.001) and OS 31 vs 9 months (P < 0.001). Well (n = 60) vs poorly differentiated NEN (n = 62): PFS 19 vs 8 months (P < 0.001) and OS 44 vs 19 months (P < 0.001). Grade 3–4 hematological or renal toxicity occurred in 17% of patients. This large multicenter cohort of patients with GEP NEN G3 treated with PRRT demonstrates promising response rates, disease control rates, PFS and OS as well as toxicity in patients with mainly progressive disease. Based on these results, PRRT may be considered for patients with GEP NEN G3.
Search for other papers by Massimo Milione in
Google Scholar
PubMed
Search for other papers by Patrick Maisonneuve in
Google Scholar
PubMed
Search for other papers by Alessio Pellegrinelli in
Google Scholar
PubMed
Search for other papers by Federica Grillo in
Google Scholar
PubMed
Search for other papers by Luca Albarello in
Google Scholar
PubMed
Search for other papers by Paola Spaggiari in
Google Scholar
PubMed
Search for other papers by Alessandro Vanoli in
Google Scholar
PubMed
Search for other papers by Giovanna Tagliabue in
Google Scholar
PubMed
Search for other papers by Eleonora Pisa in
Google Scholar
PubMed
Search for other papers by Luca Messerini in
Google Scholar
PubMed
Clinical Research Lab (CRAB), Department of Pathology and Laboratory Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
Search for other papers by Giovanni Centonze in
Google Scholar
PubMed
Search for other papers by Frediano Inzani in
Google Scholar
PubMed
Search for other papers by Aldo Scarpa in
Google Scholar
PubMed
Search for other papers by Mauro Papotti in
Google Scholar
PubMed
Search for other papers by Marco Volante in
Google Scholar
PubMed
Search for other papers by Fausto Sessa in
Google Scholar
PubMed
Search for other papers by Nicola Fazio in
Google Scholar
PubMed
University of Milan, School of Medicine, Milan, Italy
Search for other papers by Giancarlo Pruneri in
Google Scholar
PubMed
Search for other papers by Guido Rindi in
Google Scholar
PubMed
Search for other papers by Enrico Solcia in
Google Scholar
PubMed
Search for other papers by Stefano La Rosa in
Google Scholar
PubMed
Search for other papers by Carlo Capella in
Google Scholar
PubMed
Mixed adenoneuroendocrine carcinomas (MANECs) are composed of a poorly differentiated neuroendocrine carcinoma (NEC) and a non-neuroendocrine (non-NEC) neoplastic epithelial component, each representing at least 30% of the tumor. At present, prognostic factors for MANECs remain largely unexplored. We investigated the clinical-pathologic features of a large multicenter series of digestive system MANECs. Surgical specimens of 200 MANEC candidates were centrally reviewed; diagnosis was confirmed in 160 cases. While morphology, proliferation (mitotic count (MC), Ki67 index) and immunophenotype (p53, SSTR2a, beta-Catenin, Bcl-2, p16, Rb1, ALDH, mismatch repair proteins and CD117) were investigated separately in both components, genomic (TP53, KRAS, BRAF) alterations were searched for on the entire tumor. Data were correlated with overall survival (OS). MANEC sites were: 92 colorectal, 44 gastroesophageal and 24 pancreatobiliary. Median OS was 13.2 months. After adjustment for primary site, Ki67 index of the NEC component (but not of the non-NEC component) was the most powerful prognostic marker. At multivariable analysis, patients with Ki67 ≥ 55% had an 8-fold risk of death (hazard ratio (HR) 7.83; 95% confidence interval (CI) 4.17–14.7; P < 0.0001) and a median OS of 12.2 months compared to those with Ki67 < 55% (median OS 40.5 months). MC (HR 1.51; 95% CI 1.03–2.20, P = 0.04) was a weaker prognostic index. Colorectal primary site (HR 1.60; 95% CI 1.11–2.32; P = 0.01) was significantly associated with poorer survival. No single immunomarker, in either component, was statistically significant. This retrospective analysis of a large series of digestive system MANECs, showed that the NEC component, particularly its Ki67 index, was the main prognostic driver.
Search for other papers by James C Yao in
Google Scholar
PubMed
Search for other papers by Jonathan Strosberg in
Google Scholar
PubMed
Search for other papers by Nicola Fazio in
Google Scholar
PubMed
Search for other papers by Marianne E Pavel in
Google Scholar
PubMed
Search for other papers by Emily Bergsland in
Google Scholar
PubMed
Search for other papers by Philippe Ruszniewski in
Google Scholar
PubMed
Search for other papers by Daniel M Halperin in
Google Scholar
PubMed
Search for other papers by Daneng Li in
Google Scholar
PubMed
Search for other papers by Salvatore Tafuto in
Google Scholar
PubMed
Search for other papers by Nitya Raj in
Google Scholar
PubMed
Search for other papers by Davide Campana in
Google Scholar
PubMed
Search for other papers by Susumu Hijioka in
Google Scholar
PubMed
Search for other papers by Markus Raderer in
Google Scholar
PubMed
Search for other papers by Rosine Guimbaud in
Google Scholar
PubMed
Search for other papers by Pablo Gajate in
Google Scholar
PubMed
Search for other papers by Sara Pusceddu in
Google Scholar
PubMed
Search for other papers by Albert Reising in
Google Scholar
PubMed
Search for other papers by Evgeny Degtyarev in
Google Scholar
PubMed
Search for other papers by Mark Shilkrut in
Google Scholar
PubMed
Search for other papers by Simantini Eddy in
Google Scholar
PubMed
Search for other papers by Simron Singh in
Google Scholar
PubMed
Spartalizumab, a humanized anti-programmed death protein 1 (PD-1) MAB, was evaluated in patients with well-differentiated metastatic grade 1/2 neuroendocrine tumors (NET) and poorly differentiated gastroenteropancreatic neuroendocrine carcinomas (GEP-NEC). In this phase II, multicenter, single-arm study, patients received spartalizumab 400 mg every 4 weeks until confirmed disease progression or unacceptable toxicity. The primary endpoint was confirmed overall response rate (ORR) according to blinded independent review committee using response evaluation criteria in solid tumors 1.1. The study enrolled 95 patients in the NET group (30, 32 and 33 in the thoracic, gastrointestinal, and pancreatic cohorts, respectively), and 21 patients in the GEP-NEC group. The ORR was 7.4% (95% CI: 3.0, 14.6) in the NET group (thoracic, 16.7%; gastrointestinal, 3.1%; pancreatic, 3.0%), which was below the predefined success criterion of ≥10%, and 4.8% (95% CI: 0.1, 23.8) in the GEP-NEC group. In the NET and GEP-NEC groups, the 12-month progression-free survival was 19.5 and 0%, respectively, and the 12-month overall survival was 73.5 and 19.1%, respectively. The ORR was higher in patients with ≥1% PD-L1 expression in immune/tumor cells or ≥1% CD8+ cells at baseline. The most common adverse events considered as spartalizumab-related included fatigue (29.5%) and nausea (10.5%) in the NET group, and increased aspartate and alanine aminotransferases (each 14.3%) in the GEP-NEC group. The efficacy of spartalizumab was limited in this heterogeneous and heavily pre-treated population; however, the results in the thoracic cohort are encouraging and warrants further investigation. Adverse events were manageable and consistent with previous experience.
Department of Oncology and Hemato-Oncology (DIPO), University of Milan, Milan, Italy
Search for other papers by Carmine Valenza in
Google Scholar
PubMed
Search for other papers by Francesca Spada in
Google Scholar
PubMed
Search for other papers by Francesco Multinu in
Google Scholar
PubMed
Search for other papers by Lavinia Benini in
Google Scholar
PubMed
Search for other papers by Michele Borghesani in
Google Scholar
PubMed
Search for other papers by Laura Algeri in
Google Scholar
PubMed
Search for other papers by Manila Rubino in
Google Scholar
PubMed
Search for other papers by Eleonora Pisa in
Google Scholar
PubMed
Search for other papers by Lorenzo Gervaso in
Google Scholar
PubMed
Search for other papers by Chiara Alessandra Cella in
Google Scholar
PubMed
Search for other papers by Silvestro Carinelli in
Google Scholar
PubMed
Search for other papers by Simone Bruni in
Google Scholar
PubMed
Search for other papers by Gabriella Schivardi in
Google Scholar
PubMed
Department of Oncology and Hemato-Oncology (DIPO), University of Milan, Milan, Italy
Search for other papers by Giuseppe Curigliano in
Google Scholar
PubMed
Search for other papers by Vanna Zanagnolo in
Google Scholar
PubMed
Division of Gynecologic Surgery, European Institute of Oncology, IRCCS, Via Ripamonti, Milan, Italy
Search for other papers by Giovanni Aletti in
Google Scholar
PubMed
Department of Medicine and Surgery, University of Milano-Bicocca, Monza, Italy
Search for other papers by Nicoletta Colombo in
Google Scholar
PubMed
Search for other papers by Nicola Fazio in
Google Scholar
PubMed
Non-metastatic neuroendocrine carcinoma of the cervix (NECC) is a rare and aggressive disease. Lacking prospective studies, the optimal multimodal treatment approach has not yet been clearly defined. This study aims to assess the clinical outcomes of patients with non-metastatic NECC treated with surgery and (neo)adjuvant chemotherapy, according to pathologic prognostic factors and multimodal treatments received. We retrospectively examined data from patients with non-metastatic NECC candidate to receive surgery and (neo)adjuvant chemotherapy and discussed at the European Institute of Oncology’s Multidisciplinary Neuroendocrine Tumor Board, between January 2003 and December 2021. Primary endpoints were event-free survival and overall survival. A total of 27 consecutive patients were evaluated, 15 with early stage NECC and 12 with a locally advanced NECC. Eight patients received neoadjuvant and 19 adjuvant platinum-based chemotherapy; 14 received adjuvant pelvic radiotherapy, half with external-beam radiation therapy alone, and half combined with brachytherapy. No patients progressed or relapsed during (neo)adjuvant chemotherapy. The median event-free survival was 21.1 months and the median overall survival was 33.0 months. Pathological FIGO stage ≥ IIB, adjuvant external-beam radiation therapy with or without brachytherapy emerged as significant and independent prognostic factors for event-free survival. Brachytherapy was also prognostic for overall survival. Non-metastatic NECC requires a multimodal approach, mainly weighted on the FIGO stage. The addition of brachytherapy should be considered, especially in patients with locally advanced disease. Because of the scarcity of robust clinical data, treatment strategy should be discussed in multidisciplinary board, taking into account patient.
Search for other papers by Nicola Fazio in
Google Scholar
PubMed
Molecular Medicine Program, University of Pavia, Pavia, Italy
Search for other papers by Lorenzo Gervaso in
Google Scholar
PubMed
Search for other papers by Thorvardur R Halfdanarson in
Google Scholar
PubMed
Search for other papers by Mohamad Sonbol in
Google Scholar
PubMed
Search for other papers by Rachel A Eiring in
Google Scholar
PubMed
Search for other papers by Sara Pusceddu in
Google Scholar
PubMed
Search for other papers by Natalie Prinzi in
Google Scholar
PubMed
Search for other papers by Benedetta Lombardi Stocchetti in
Google Scholar
PubMed
Search for other papers by Simona Grozinsky-Glasberg in
Google Scholar
PubMed
Search for other papers by David J Gross in
Google Scholar
PubMed
Search for other papers by Thomas Walter in
Google Scholar
PubMed
Search for other papers by Patrick Robelin in
Google Scholar
PubMed
Search for other papers by Catherine Lombard-Bohas in
Google Scholar
PubMed
Search for other papers by Samuele Frassoni in
Google Scholar
PubMed
Search for other papers by Vincenzo Bagnardi in
Google Scholar
PubMed
Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy
Search for other papers by Lorenzo Antonuzzo in
Google Scholar
PubMed
Search for other papers by Clotilde Sparano in
Google Scholar
PubMed
Search for other papers by Sara Massironi in
Google Scholar
PubMed
Search for other papers by Fabio Gelsomino in
Google Scholar
PubMed
Search for other papers by Alberto Bongiovanni in
Google Scholar
PubMed
Search for other papers by Nicoletta Ranallo in
Google Scholar
PubMed
Search for other papers by Salvatore Tafuto in
Google Scholar
PubMed
Search for other papers by Maura Rossi in
Google Scholar
PubMed
Search for other papers by Mauro Cives in
Google Scholar
PubMed
Search for other papers by Ibrahim Rasul Kakil in
Google Scholar
PubMed
Search for other papers by Hytam Hamid in
Google Scholar
PubMed
Search for other papers by Alessandra Chirco in
Google Scholar
PubMed
Search for other papers by Michela Squadroni in
Google Scholar
PubMed
Search for other papers by Anna La Salvia in
Google Scholar
PubMed
Search for other papers by Jorge Hernando in
Google Scholar
PubMed
Search for other papers by Johannes Hofland in
Google Scholar
PubMed
Search for other papers by Anna Koumarianou in
Google Scholar
PubMed
Search for other papers by Sabrina Boselli in
Google Scholar
PubMed
Search for other papers by Darina Tamayo in
Google Scholar
PubMed
Search for other papers by Cristina Mazzon in
Google Scholar
PubMed
Search for other papers by Manila Rubino in
Google Scholar
PubMed
Search for other papers by Francesca Spada in
Google Scholar
PubMed
We conducted a retrospective/prospective worldwide study on patients with neuroendocrine neoplasms (NENs) and a molecularly proven SARS-CoV-2 positivity. Preliminary results regarding 85 patients of the INTENSIVE study have been published in 2021. Now we are reporting the 2-year analysis.Here, we are reporting data from consecutive patients enrolled between 1 June 2020, and 31 May 2022. Among the 118 contacted centers, 25 were active to enroll and 19 actively recruiting at the time of data cut-off for a total of 280 patients enrolled. SARS-CoV-2 positivity occurred in 47.5% of patients in 2020, 35.1% in 2021, and 17.4% in 2022. The median age for COVID-19 diagnosis was 60 years. Well-differentiated tumors, non-functioning, metastatic stage, and gastroenteropancreatic (GEP) primary sites represented most of the NENs. COVID-19-related pneumonia occurred in 22.8% of the total, with 61.3% of them requiring hospitalization; 11 patients (3.9%) needed sub-intensive or intensive care unit therapies and 14 patients died (5%), in 11 cases (3.9%) directly related to COVID-19. Diabetes mellitus and age at COVID-19 diagnosis > 70 years were significantly associated with COVID-19 mortality, whereas thoracic primary site with COVID-19 morbidity. A significant decrease in both hospitalization and pneumonia occurred in 2022 vs 2020. In our largest series of NEN patients with COVID-19, the NEN population is similar to the general population of patients with NEN regardless of COVID-19. However, older age, non-GEP primary sites and diabetes mellitus should be carefully considered for increased COVID-19 morbidity and mortality. Relevant information could be derived by integrating our results with NENs patients included in other cancer patients with COVID-19 registries.
Search for other papers by Sara Pusceddu in
Google Scholar
PubMed
Search for other papers by Francesco Barretta in
Google Scholar
PubMed
Search for other papers by Annalisa Trama in
Google Scholar
PubMed
Search for other papers by Laura Botta in
Google Scholar
PubMed
Search for other papers by Massimo Milione in
Google Scholar
PubMed
Search for other papers by Roberto Buzzoni in
Google Scholar
PubMed
University of Milan, Milan, Italy
Search for other papers by Filippo De Braud in
Google Scholar
PubMed
Liver Surgery, Transplantation and Gastroenterology, University of Milan and Istituto Nazionale Tumori Fondazione IRCCS, ENETS Center of Excellence, Milano, Milan, Italy
Search for other papers by Vincenzo Mazzaferro in
Google Scholar
PubMed
Search for other papers by Ugo Pastorino in
Google Scholar
PubMed
Search for other papers by Ettore Seregni in
Google Scholar
PubMed
Search for other papers by Luigi Mariani in
Google Scholar
PubMed
Search for other papers by Gemma Gatta in
Google Scholar
PubMed
Search for other papers by Maria Di Bartolomeo in
Google Scholar
PubMed
Search for other papers by Daniela Femia in
Google Scholar
PubMed
Search for other papers by Natalie Prinzi in
Google Scholar
PubMed
Search for other papers by Jorgelina Coppa in
Google Scholar
PubMed
Search for other papers by Francesco Panzuto in
Google Scholar
PubMed
Search for other papers by Lorenzo Antonuzzo in
Google Scholar
PubMed
Search for other papers by Emilio Bajetta in
Google Scholar
PubMed
Search for other papers by Maria Pia Brizzi in
Google Scholar
PubMed
Search for other papers by Davide Campana in
Google Scholar
PubMed
Search for other papers by Laura Catena in
Google Scholar
PubMed
Search for other papers by Harry Comber in
Google Scholar
PubMed
Search for other papers by Fiona Dwane in
Google Scholar
PubMed
Search for other papers by Nicola Fazio in
Google Scholar
PubMed
Search for other papers by Antongiulio Faggiano in
Google Scholar
PubMed
Search for other papers by Dario Giuffrida in
Google Scholar
PubMed
Search for other papers by Kris Henau in
Google Scholar
PubMed
Search for other papers by Toni Ibrahim in
Google Scholar
PubMed
Search for other papers by Riccardo Marconcini in
Google Scholar
PubMed
Search for other papers by Sara Massironi in
Google Scholar
PubMed
Search for other papers by Maja Primic Žakelj in
Google Scholar
PubMed
Search for other papers by Francesca Spada in
Google Scholar
PubMed
Search for other papers by Salvatore Tafuto in
Google Scholar
PubMed
Search for other papers by Elizabeth Van Eycken in
Google Scholar
PubMed
Search for other papers by Jan Maaten Van der Zwan in
Google Scholar
PubMed
Search for other papers by Tina Žagar in
Google Scholar
PubMed
Search for other papers by Luca Giacomelli in
Google Scholar
PubMed
Search for other papers by Rosalba Miceli in
Google Scholar
PubMed
Search for other papers by NEPscore Working Group in
Google Scholar
PubMed
No validated prognostic tool is available for predicting overall survival (OS) of patients with well-differentiated neuroendocrine tumors (WDNETs). This study, conducted in three independent cohorts of patients from five different European countries, aimed to develop and validate a classification prognostic score for OS in patients with stage IV WDNETs. We retrospectively collected data on 1387 patients: (i) patients treated at the Istituto Nazionale Tumori (Milan, Italy; n = 515); (ii) European cohort of rare NET patients included in the European RARECAREnet database (n = 457); (iii) Italian multicentric cohort of pancreatic NET (pNETs) patients treated at 24 Italian institutions (n = 415). The score was developed using data from patients included in cohort (i) (training set); external validation was performed by applying the score to the data of the two independent cohorts (ii) and (iii) evaluating both calibration and discriminative ability (Harrell C statistic). We used data on age, primary tumor site, metastasis (synchronous vs metachronous), Ki-67, functional status and primary surgery to build the score, which was developed for classifying patients into three groups with differential 10-year OS: (I) favorable risk group: 10-year OS ≥70%; (II) intermediate risk group: 30% ≤ 10-year OS < 70%; (III) poor risk group: 10-year OS <30%. The Harrell C statistic was 0.661 in the training set, and 0.626 and 0.601 in the RARECAREnet and Italian multicentric validation sets, respectively. In conclusion, based on the analysis of three ‘field-practice’ cohorts collected in different settings, we defined and validated a prognostic score to classify patients into three groups with different long-term prognoses.